DESCRIPTION: The human microbiota contributes to our normal postnatal development and plays a significant role in defining our physiology. To understand the role of microbiota in human health and disease, we propose to study the skin microbiome in pilosebaceous units (hair follicles) and its association with acne. Acne is one of the most common skin diseases. Although its etiology still needs to be defined, a bacterial factor has been suggested in the development of the disease. In fact, antibiotic therapy targeting Propionibacterium acnes has been a mainstay treatment for more than 30 years. Our preliminary study shows that the microcomedone, a specialized skin compartment where acne arises, has a tractable microbiome, with a single dominant species, P. acnes. This system offers a unique advantage allowing in-depth analysis of a human microbiome at the subspecies level by DNA sequencing, whereas the microbial communities at many other body sites are just too complicated to deconvolute even at the species level. In our preliminary study, we find that P. acnes strains in acne patients appear to be clonal, with distinct nucleotide signatures of 16S rDNA sequences, whereas P. acnes strains from normal individuals are much more diverse and scatter through many lineages. This indicates that the microbiome associated with acne offers promise for understanding the correlation between the composition of the microbiome and human health and disease. In this project, we plan to investigate in three directions the microbiome associated with acne. First, we plan to investigate the strain diversity of P. acnes in a disease cohort and normal cohort and examine whether certain strains of P. acnes are correlated with disease. Second, we plan to investigate the non-P. acnes microbes in microcomedones and disease lesions and examine whether they correlate with acne pathogenesis. These microbes include small eukaryotes, bacteria, viruses and bacteriophages. Third, we will examine the interactions between the microbes and the host by transcriptional profiling of both the microbiota and the host. By the end of the first year of this project, we plan to complete the sequencing of 10,000 16S rDNA clones and 48 full genomes of P. acnes strains. We believe our analysis of the microbiome of the pilosebaceous units will shed light on the microbial composition of the skin biota and its relation to acne. PUBLIC HEALTH RELEVANCE: Acne affects 17 million Americans, more than 80% of the people of age 12-24. The goal of this project is to investigate the relationship between acne and the microbiota residing underneath the surface of the human skin. Success in this project may lead to the development of new effective therapeutic strategies for treatment of acne.